Calcified tissue facing preparation containing antimicrobial agent

ABSTRACT

The present invention provides a calcified tissue facing preparation characterized by having a polymerizable resin, and an antimicrobial agent of the formula:  
                 
 
     where R 1  is a hydrocarbon radical having between 1 and 16 carbon atoms, n is an integer between 1 and 8 inclusive and X is a halogen atom selected from fluorine, chlorine or bromine. It is appreciated that R 1  includes unsaturated hydrocarbon radicals, as well as heteroatom containing radicals. Preferably, the molecule of Formula (I) is associated with an adduct species. At least one of glutaraldehyde or a chelating agent are added to enhance the preparation characteristics.

RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. patentapplication Serial No. 09/806,041 filed Mar. 26, 2001, which claimspriority of PCT Application Serial No. PCT/US99/21265 filed Sep. 23,1999, which claims the benefit of U.S. Provisional Patent ApplicationSerial No. 60/101,655 filed Sep. 24, 1998, which are incorporated hereinby reference.

FIELD OF THE INVENTION

[0002] This invention relates to compositions for sealing calcifiedtissue substrates to inhibit infection and promote subsequentrestorative material bonding; in particular, the invention is tailoredto dentinal tubules, in order to prevent dentinal hypersensitivity andfurther to promote effective bonding of subsequent restorative dentalmaterials such as amalgams, composites, resins and cementitiousmaterials.

BACKGROUND OF THE INVENTION

[0003] Dental caries are a common disease of modem humankind. Thetreatment of dental caries involves the removal of the carious lesion bya number of means including mechanical drilling and light ablation. Theensuing removal of dentin brings the dental nerve endings containedwithin the pulp into proximity with the mouth. Filling the resultingcavity in order to isolate the nerve endings leaves the toothsusceptible to thermal hypersensitivity via thermal conduction throughthe filling as well as bacterial infection. Bacterial colonization ofthe filled cavity induces further caries formation and hypersensitivity.

[0004] Currently, polymeric resinous materials are widely used to fillcavities, as well as in cosmetic dentistry and corrective dentalstructures including brackets, braces, veneers, onlays, crowns, and thelike. In adhering dental structures to tooth enamel, there are minorproblems with thermal or bacterial hypersensitivity.

[0005] In contrast, when the dentin of a tooth is exposed as a result ofcervical erosion or tooth decay, changes occur in the physical structureof the dentin. Whereas tooth enamel is a densified, nonporous substance,dentin is characterized by a porous structure containing thousands ofdentinal tubules. The dentinal tubules extend outward from the toothpulp and terminate at or before the tooth enamel. These tubules containpressurized pulp fluid which seeps from the pulp when the ends of thetubules are exposed. Collagen fibers are also associated with thetubules.

[0006] Typically, neither cervical erosion nor drilling of dentindirectly exposes the ends of the dental tubules. Cervical erosionsurfaces are characterized by irregularities and hemisphericalprotrusions. The dentinal tubules are mostly filled with inorganicmaterial although some maintain openings of various sizes. Drilling ofdentin creates a debris field which is characterized by weakened andcracked dentin. Since the debris field is structurally unsound, adheringa restorative material thereto creates a weak filling.

[0007] The cleaning of dentin prior to bonding a material thereto isthus highly advantageous. Typically, acid etching is used to decalcifythe surface dentin and enlarge the openings of the tubules. Acid etchingleaves behind the protruding collagen fibers that are associated withthe dentinal tubes. Chelating agents such as EDTA are known to helpdissolve calcified deposits associated with a dentinal tubule opening.These collagen fibers represent a substrate for bacterial colonizationas well as a hydrophilic surface for the bonding of a polymeric resinousmaterial. The acid etching solution is typically a 20-50% by weightsolution of phosphoric acid, but also includes citric and nitric acids.

[0008] A number of facing preparations are currently in use to seal anddisinfect a dentin surface following acid etching. These preparationstypically include a monomeric resin capable of cross linking to thecollagen fibers. Glutaraldehyde (GLUMA, Heraeus Kulzer, Inc.) andbenzalkonium chloride (Healthdent, Inc.) are added as antimicrobials.These prior art antimicrobials are limited in their efficacy.Glutaraldehyde polymerizes in water and thereby the effective dosagesdecrease. Furthermore, glutaraldehyde is a known irritant as well asantiseptic and thereby may induce the dental hypersensitivity which thefacing preparation is designed to prevent. Benzalkonium chloride is apotent antimicrobial yet is incompatible with anionic detergents such assoap, as well as with nitrates. While the benzalkonium cation iselectrically attracted to dentin, stearic considerations prevent optimalinteractions between the radical and dentinal tubules.

SUMMARY OF THE INVENTION

[0009] The present invention provides a facing preparation compositioncontaining a polymerizable resin and an antimicrobial agent having theformula:

[0010] where R₁ is a hydrocarbon having between 1 and 16 carbon atoms, nis an integer between 1 and 8 inclusive, R₂ is selected from the groupconsisting of halophenyl and 2-ethylhexyl. The antimicrobial agent isdelivered in the form of an organic salt, with the anionic speciesillustratively selected from: acetate, gluconate, propionate, andacrylate. Optionally, a solvent is also provided to promote diffusion ofthe other composition components into a substrate. Solvents operative inthe present invention illustratively include: methanol, water, acetone,methyl ethyl ketone, and isopropanol.

[0011] The facing preparation composition also includes 0.1 to 20% byweight glutaraldehyde as a secondary and synergistically actingantimicrobial. Alternatively, a chelating agent is present in the facingpreparation in order to complex calcified deposits associated withdentinal tubule openings so as to prepare a clean dentinal tubulebonding surface.

[0012] An antimicrobial oral rinse contains the antimicrobial agentpresent at greater than 0.2% by weight in a buccal cavity compatiblesolvent containing a chelating agent and excluding the polymerizableresin of the facing preparation composition.

DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention pertains to compositions for facing anddisinfecting a calcified tissue structure. The facing preparation of thepresent invention inhibits thermal and microbial hypersensitivity inproximal nerves of the organism. The facing preparation of the presentinvention also promotes bonding of a subsequent structural sealing layerto the calcified tissue. The term “calcified tissue” as used herein isdefined to mean periosteum, cortical bone, tooth enamel, cementum,dentin, and pulp. The present invention has particular utility in facingand disinfecting exposed dentin for subsequent bonding of additionalrestorative dental materials.

[0014] Optionally, calcified tissue substrates are etched by meansconventional to the art, prior to application of a facing preparation ofthe instant invention. Acid etching generally involves application ofmineral acids illustratively including phosphoric, nitric, citric andhydrofluoric acids. It is appreciated that mechanical etching using anabrasive grit is also operative herein. Following etching, extraneousacid and debris are removed from the substrate by irrigating the etchedsubstrate with water. The substrate is then blotted or evaporativelydried by means illustratively including an air jet.

[0015] The facing preparation of the instant invention contains apolymerizable resin. The term “polymerizable resin” as defined hereinmeans either a hydrophilic polymerizable compound having at least onehydroxyl moiety therein, a hydrophobic polymerizable hydrocarbon, or apolymerizable compound having both a hydrophobic and a hydrophilicmoiety therein. Polymerizable resins operative within the presentinvention illustratively include hydroxyalkyl methacrylates,hydroxyalkyl acrylates, alkyl methacrylates, alkyl acrylates, polyhydricalcohols, mixtures thereof, substituted derivatives thereof and thelike. Specific polymerizable resins operative within the presentinvention illustratively include 2-hydroxymethyl methacrylate (HMMA),2-hydroxyethyl methacrylate (HEMA), bisphenol-A-glycidyl methacrylateprepolymer (bis-GMA), N-phenylglycine/glycidyl methacrylate (NPG-GMA),bis(glycerol dimethacrylate) phosphate, glycerol methacrylate, methylacrylate, triethylene glycol dimethacrylate and the like. Preferably,hydrophilic resins such as HMMA and HEMA are used in facing preparationsof the present invention which are tailored to treatment of inherentlymoist substrates, such as dentin. The facing preparations of the presentinvention preferably include a polymerizable resin present in amountsranging from about 10-90% by weight relative to the total facingpreparation weight. More preferably, the polymerizable resin is includedin the facing preparation in amounts from 20-60 weight percent relativeto the total facing preparation weight. Most preferably, thepolymerizable resin is included in the facing preparation in amountsfrom 30-50 weight percent relative to the total facing preparationweight.

[0016] The facing preparation of the present invention optionallyfurther includes a solvent. The solvent promoting diffusion of thefacing preparation into microscopic pores and crevices of the substrate.The solvent is chosen to impart solubility on the polymerizable resinused in a particular facing preparation. In those instances where theosteoporotic substrate is dentin, hydrophilic solvents are preferred.Solvents operative within a facing preparation of the present inventionillustratively include: ethanol, water, acetone, methyl ethyl ketone,and isopropanol. The solvent is preferably present in the facingpreparation in amounts ranging from 10-90% relative to the total facingpreparation weight. More preferably, the solvent is included in thefacing preparation in an amount ranging from 20-80% by weight relativeto the total facing preparation weight. Most preferably, the solvent isincluded in the facing preparation in an amount ranging from 30-70% byweight relative to the total facing preparation weight. It isappreciated that a miscible mixture of solvents is also operativeherein.

[0017] The facing preparation of the present invention also includes anantimicrobial agent of the formula:

[0018] where R₁ is a hydrocarbon radical having between 1 and 16 carbonatoms, n is an integer between 1 and 8 inclusive and R₂ is selected fromhalophenyl and 2-ethylhexyl. It is appreciated that R₁ includesunsaturated hydrocarbon radicals, as well as heteroatom containingradicals. Preferably, the molecule of Formula (I) is associated with anadduct species. The adduct species being selected to promote solubilityin the facing preparation. Adduct species operative in the presentinvention illustratively include: acetate, gluconate, propionate, andacrylate. Preferably, R₁ is a saturated hydrocarbon. Preferably, R₁ hasbetween 1 and 6 carbon atoms. Preferably, the halophenyl ischlorophenyl. More preferably, the halophenyl is para-halophenyl.Specific antimicrobial agents of Formula (I) illustratively include:alexidine, chlorhexidine, alexidine gluconate, chlorhexidine gluconate,alexidine acetate, chlorhexidine acetate and chlorhexidine digluconate.

[0019] Both alexidine and chlorhexidine are effective antimicrobialsagainst a wide range of vegative gram positive and gram negativeorganisms. The facing preparation of the present invention is preferablybuffered to pHs ranging from about 5-9. More preferably, the presentinvention is buffered to pHs ranging from 6-9.

[0020] The antimicrobial agent of Formula (I) is present in an inventivefacing formulation between 0.1 and 10% by weight. Preferably, theantimicrobial agent (I) is present from 0.2 to 5% by weight.

[0021] A synergistic effect is noted in the present invention based onthe dual action of an antimicrobial agent of Formula (I) in combinationwith glutaraldehyde. While the specific mechanism remains unclear, acumulative improvement is observed in facing properties uponconsideration of the properties of bond strength, tissue irritation, andrestoration sensitivity. Typically, glutaraldehyde is present at 0.1 to20% by weight and at a ratio of between 1:5 and 5:1 relative to theantimicrobial agent of Formula (I) subject to the quantity ofglutaraldehyde present. Preferably, the glutaraldehyde to antimicrobialagent of Formula (I) ratio is between 1:3 and 3:1. Still morepreferably, the antimicrobial agent of Formula (I) is present at between1 and 5% by weight. In a most preferred embodiment, the antimicrobialagent of Formula (I) is present at 3% by weight and glutaraldehyde ispresent at 1 to 5% by weight, with a 1:1 ratio therebetween being highlyeffective.

[0022] Optionally, an additive biocide is introduced into thecompositions of the present invention. Benzalkonium chloride isoperative as an additive in the present invention compositions between0.1 and 10% by weight of the total composition weights. It isappreciated that other additives, adjuvants, surfactants, stabilizers,dyes, and emulsifiers are also added optionally to the presentinvention. In particular, fluoride solution present to about 0.5% byweight is a well established wash effective against dental caries.

[0023] In an alternate embodiment of the present invention, a chelatingagent is introduced into an inventive facing preparation, independent ofthe presence of glutaraldehyde therein. The chelating agent is dissolvedin the inventive facing preparation and is capable of complexing thoseions which are present in a calcified deposit associated with a dentinaltubule opening.

[0024] Suitable chelating agents useful in the present inventionillustratively include ethylenediaminetetraacetic acid (EDTA),diethylenetriaminepentaacetic acid (DTPA), nitrilotriacetic acid (NTA),iminodiacetic acid (IDA), iminotriacetic acid (ITA), ethylenediamine(En), N,N′-diethylenediamine (Den), diethylenetriamine (DTN),diethylenetetramine (Trien), triaminotriethylene amine,propylenediamine, glycolic acid, hydroxybutyric acid, salicylic acid,benzoic acid, mixtures thereof and other polydentate chelating agentswhich are compatible with the buccal cavity and active in bindingdivalent cations such as Ca²⁺, Mg²⁺, Fe²⁺, and the like. Binding ofcalcium ions a preferred function of a chelating agent according to thepresent invention. Preferably, the chelating agent of the presentinvention contains carboxylate moieties. More preferably, the chelatingagent is EDTA. A chelating agent of the present invention is dissolvedin an inventive facing preparation in an amount of about 3% by totalweight to solution saturation at 20° C. Chelating agent solutions aretypically between 3% and 20% by weight of the facing preparation.Preferably, the chelating agent is present between 7% and 18% by totalweight; more preferably, at between 9% and 14% by total weight.

[0025] It is appreciated that an acid is optionally introduced to modifythe buffered pH of the facing preparation and modify the chelationcharacteristics of the inventive preparation. Suitable pH lowering acidsuseful in the present invention illustratively include ascorbic, acetic,propionic, formic, succinic, hydrochloric, sulfuric, nitric, phosphoric,orthophosphoric and citric.

[0026] In another embodiment, solutions of the antimicrobial agent (I)are provided which lack the polymerizable resin. This solution hasutility as an oral rinse to cleanse the buccal cavity and in particulartubules prior to application of conventional dental structures. Whilesuch rinses have previously been utilized having between about 0.12% to0.20% chlorohexidine, considerably more effective antimicrobialformulations are disclosed herein. An antimicrobial rinse according tothe present invention includes between 0.2 and 10% by weight ofantimicrobial based on total solution weight. Preferably, the rinsecontains 0.2 to 5% antimicrobial. More preferably, the rinse contains asolvent of water, acetone or ethanol or mixtures thereof.

[0027] It is appreciated that the facing preparation of the presentinvention may also include other conventional microbial agents whichhave a complementary antimicrobial spectrum to those of Formula (I). Themicrobial agents of Formula (I) are particularly effective over timeowing to charge interactions between the substrate and the agents ofFormula (I).

[0028] The following examples are given for the purpose of illustratingvarious embodiments of the invention and are not meant to limit thepresent invention in any way.

EXAMPLE 1

[0029] A dentin facing preparation is formed from the followingcomponents: % by Weight of Component the Total Preparation HEMA 45Ethanol 50 Chlorhexidine 5

[0030] Dentin is etched with a 40% phosphoric acid solution. The etcheddentin is irrigated with water and dried with an air jet. The facingpreparation is mixed and swabbed onto the dentin surface and allowed toair dry for about 20 seconds. The facing preparation is overlayered witha HEMA based polymerizable sealant Prodigy with Optibond Solo (KerrCorp.). A strong filling persisted for greater than 6 months. Thepatient experienced no hypersensitivity associated with exposing thefilled dentin cavity to hot water, bite pressure, or ice. The process isrepeated and found to be repeatable with comparable sealant strengths.

EXAMPLE 2

[0031] A dentin facing preparation is formed of the followingcomponents: % by Weight of Component the Total Preparation HMMA 40 Water59 Chlorhexidine gluconate 1

[0032] This facing preparation composition behaves similarly to thecomposition of the primer in Example 1.

EXAMPLE 3

[0033] A dentin facing preparation is formed from the followingcomponents: % by Weight of Component the Total Preparation HEMA 50Ethanol 30 Water 10 Chlorhexidine acetate hydrate 10

[0034] This facing preparation composition behaves similarly to thecomposition of the facing preparation in Example 1.

EXAMPLE 4

[0035] A dentin facing preparation is formed from the followingcomponents: % by Weight of Component the Total Preparation HEMA 40 Water50 Alexidine gluconate 5 Benzalkonium chloride 5

[0036] This facing preparation composition behaves similarly to thecomposition of the facing preparation in Example 1.

EXAMPLE 5

[0037] A cementum facing preparation is formed from the followingcomponents: % by Weight of Component the Total Preparation Glycerolmethacrylate 28 Ethanol 18 Water 48 Chlorhexidine gluconate 6

[0038] The facing preparation prevented cervical infection and affordedgood bond strength when a subsequent bis-GMA sealant resin is applied.

EXAMPLE 6

[0039] A cortical bone facing preparation is formed from the followingcomponents: % by Weight of Component the Total Preparation HMMA 55 Water41 Chlorhexidine 3 Ciprofloxin 1

[0040] The facing preparation promoted adhesion to a cyanomethacrylatebased bonding material.

EXAMPLE 7

[0041] The in vitro tensile bond strength of a conventional toothbonding composite Prodigy with Optibond Solo (Kerr Corp.) is measuredwith and without the dentin facing preparation of Example 1. Bondstrength and failure modes are determined for bonding to superficial anddeep dentin sites. Bond Strength, MPa Superficial Deep Dentin DentinControl 27 ± 13 28 ± 8 With facing preparation 36 ± 11 29 ± 6 of Example1 Failure Sites, % Superficial Deep Dentin Dentin Control 54A/46C44A/26C/30T With facing preparation 22A/68C/10T 46A/48C/6T of Example 1

[0042] where A is an adhesive failure at the tooth-composite surface, Cis cohesive failure in the composite and T is a cohesive failure in thedentin.

EXAMPLE 8

[0043] Standardized cultures of Strept. mutans are grown in petri dishesand subjected to 30 second submersion in 20 milliliters of variousconcentration rinses of aqueous chlorohexidine. A 0.04% chlorohexidinesolution and water serve as controls. Thereafter, the petri dishes areincubated and colony members counted after 48 hours. ChlorohexidineColony Member Concentration (wt. %) After Rinse 0 196 0.04 26 0.2 0 0.51 1.0 1 2.0 0 5.0 2 10.0 0

EXAMPLE 9

[0044] A dentin facing preparation is formed from the followingcomponents: % by Weight of Component the Total Preparation HEMA 45Ethanol 49 Chlorhexidine gluconate 3 Glutaraldehyde 3

[0045] The procedure of Example 1 was followed with comparable resultsexcept bond strengths were higher relative to the preparation of Example1.

EXAMPLE 10

[0046] A dental facing preparation is formed of the followingcomponents: % by Weight of Component the Total Preparation HMMA 40 Water47 EDTA 10 Chlorhexidine acetate hydrate 3

[0047] This facing preparation behaved similarly to the compositionprovided in Example 2 except with higher bond strengths.

[0048] Those skilled in the art will readily appreciate from theforegoing description that the broad teachings of the present inventioncan be implemented in a variety of forms. Therefore, while thisinvention has been described in connection with particular examplesthereof, the true scope of the invention should not be so limited sinceother modifications will become apparent to the skilled practitionerupon considering the specification and following claims.

1. A facing preparation composition comprising: a polymerizable acrylateresin; 0.1 to 10 weight percent of an antimicrobial agent having theformula:

where R₁ is a hydrocarbon having between 1 and 16 carbon atoms, n is aninteger between 1 and 8 inclusive, R₂ is selected from the groupconsisting of halophenyl and 2-ethylhexyl, said antimicrobial agentbeing coupled to a solubility promoting adduct species; and 0.1 to 20%by weight glutaraldehyde:
 2. The facing preparation composition of claim1 wherein said antimicrobial is chlorhexidine.
 3. The facing preparationcomposition of claim 1 wherein said antimicrobial is alexidine.
 4. Thefacing preparation composition of claim 1 wherein said solubilitypromoting adduct species is selected from the group consisting of:acetate, gluconate, propionate, and acrylate.
 5. The facing preparationcomposition of claim I wherein said antimicrobial is present from 1 to 5total weight percent.
 6. The facing preparation of claim 1 whereinglutaraldehyde is present from 1 to 5% by weight.
 7. The facingpreparation composition of claim 5 wherein glutaraldehyde is present inan amount of less than 20 weight percent and such that the weight ratiobetween said antimicrobial agent and glutaraldehyde is between 1:5 and5:1.
 8. The facing preparation composition of claim 1 further comprisinga chelating agent.
 9. The facing preparation composition of claim 8wherein said chelating agent is present between 3 and 20% by weight. 10.The facing preparation composition of claim 8 wherein said chelatingagent is selected from the group consisting of:ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid,nitrilotriacetic acid, iminodiacetic acid, iminotriacetic acid,ethylenediamine, N,N′-diethylenediamine, diethylenetriamine,diethylenetetramine, triaminotriethylene amine, propylenediamine,glycolic acid, hydroxybutyric acid, salicylic acid, benzoic acid,mixtures thereof.
 11. The facing preparation composition of claim 8wherein said chelating agent is ethylenediaminetetraacetic acid.
 12. Afacing preparation composition comprising: a polymerizable acrylateresin; 0.1 to 10% by weight of an antimicrobial agent having theformula:

where R₁ is a hydrocarbon having between 1 and 16 carbon atoms, n is aninteger between 1 and 8 inclusive, R₂ is selected from the groupconsisting of halophenyl and 2-ethylhexyl, said antimicrobial agentbeing coupled to a solubility promoting adduct species; and a chelatingagent capable of complexing ions present in a calcified depositassociated with a dental surface.
 13. The facing preparation compositionof claim 12 wherein said antimicrobial is chlorhexidine.
 14. The facingpreparation composition of claim 12 wherein said antimicrobial isalexidine.
 15. The facing preparation composition of claim 12 whereinsaid solubility promoting adduct species is selected from the groupconsisting of: acetate, gluconate, propionate, and acrylate.
 16. Thefacing preparation composition of claim 12 wherein said antimicrobial ispresent from 1 to 5 total weight percent.
 17. The facing preparationcomposition of claim 12 further comprising a chelating agent.
 18. Thefacing preparation composition of claim 17 wherein said chelating agentis present between 3 and 20% by weight.
 19. The facing preparationcomposition of claim 17 wherein said chelating agent is selected fromthe group consisting of: ethylenediaminetetraacetic acid,diethylenetriaminepentaacetic acid, nitrilotriacetic acid, iminodiaceticacid, iminotriacetic acid, ethylenediamine, N,N′-diethylenediamine,diethylenetriamine, diethylenetetramine, triaminotriethylene amine,propylenediamine, glycolic acid, hydroxybutyric acid, salicylic acid,benzoic acid, mixtures thereof.
 20. The facing preparation compositionof claim 12 further comprising 0.1 to 20% by weight glutaraldehyde. 21.The facing preparation composition of claim 12 wherein said chelatingagent is present from 9 to 14 total weight percent.
 22. The facingpreparation composition of claim 12 further comprising a solventselected from the group consisting of: water, ethanol, acetone, andmixtures thereof.
 23. The facing preparation composition of claim 12further comprising a pH lowering acid.
 24. A commercial packagecomprising a polymerizable acrylate resin, an antimicrobial agent ofFormula (I) according to claim 1 along with at least one componentselected from the group consisting of: glutaraldehyde and a chelatingagent together with instructions for the use thereof as a dental facingpreparation.
 25. A process for cleansing a dentin tubule prior toapplication of a dental structure, the process comprising the steps of:(a) swabbing a tooth surface with an antimicrobial mixture, the mixturecomprising at least 0.2% by weight of an antimicrobial agent having theformula:

where R₁ is a hydrocarbon having between 1 and 16 carbon atoms, n is aninteger between 1 and 8 inclusive, R₂ is selected from the groupconsisting of halophenyl and 2-ethylhexyl, and a buccal cavitycompatible solvent, and 3 to 20 percent by weight of a chelating agent;and (b) applying the dental structure.
 26. The process of claim 25wherein said antimicrobial agent is present from 0.2 to 5% by weight.27. The process of claim 25 wherein said antimicrobial of Formula (I) iscoupled to an adduct species, said species selected from the groupconsisting of: acetate, gluconate, propionate, and acrylate.
 28. Theprocess of claim 25 wherein said chelating agent is selected from thegroup consisting of: ethylenediaminetetraacetic acid,diethylenetriaminepentaacetic acid, nitrilotriacetic acid, iminodiaceticacid, iminotriacetic acid, ethylenediamine, N,N′-diethylenediamine,diethylenetriamine, diethylenetetramine, triaminotriethylene amine,propylenediamine, glycolic acid, hydroxybutyric acid, salicylic acid,benzoic acid, mixtures thereof.
 29. The process of claim 26 wherein saidchelating agent is ethylenediaminetetraacetic acid.
 30. A process forpreparing a tooth for a dental procedure comprising the steps of: (a)priming a tooth for application of a dental facing composition; (b)providing the dental facing composition wherein the compositioncomprises a polymerizable acrylate resin, from 0.1 to 10 weight percentof an antimicrobial agent having the formula:

where R₁ is a hydrocarbon having between 1 and 16 carbon atoms, n is aninteger between 1 and 8 inclusive, R₂ is selected from the groupconsisting of halophenyl and 2-ethylhexyl, said antimicrobial agent iscoupled to a solubility promoting adduct species, and at least one of:0.1 to 10 weight percent glutaraldehyde or from 3 to 20 weight percentof a chelating agent; and (c) applying the dental facing composition tothe tooth surface, wherein the application of the dental facingcomposition prepares the tooth for the dental procedure.